ClinVar Miner

Submissions for variant NM_001038603.3(MARVELD2):c.1331+2T>C

dbSNP: rs772048719
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001091915 SCV001248194 pathogenic not provided 2016-10-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091915 SCV001480105 pathogenic not provided 2021-02-01 criteria provided, single submitter clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375176 SCV001571782 likely pathogenic Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PVS1_Strong, PM2_Moderate, PM3_Supporting
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV001799517 SCV001739311 pathogenic Autosomal recessive nonsyndromic hearing loss 49 2020-10-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001091915 SCV003525828 pathogenic not provided 2022-06-19 criteria provided, single submitter clinical testing This variant is also known as TRIC IVS4+2T>C. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 17186462). ClinVar contains an entry for this variant (Variation ID: 871776). Disruption of this splice site has been observed in individual(s) with autosomal recessive deafness (PMID: 22097895, 25666562). This variant is present in population databases (rs772048719, gnomAD 0.02%). This sequence change affects a donor splice site in intron 4 of the MARVELD2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MARVELD2 are known to be pathogenic (PMID: 17186462).
3billion RCV001799517 SCV003841765 pathogenic Autosomal recessive nonsyndromic hearing loss 49 2023-02-23 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000871776 / PMID: 17186462 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV001091915 SCV005325152 pathogenic not provided 2023-11-03 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 34426522, 34238775, 32445360, 26561413, 18084694, 17186462, 25652404, 32884365, 30303587, 25666562, 22097895, 25885414, 30872814, 29752989, 34440452, 32847582, 37108562, 30406641)
OMIM RCV001799517 SCV000021406 pathogenic Autosomal recessive nonsyndromic hearing loss 49 2008-01-01 no assertion criteria provided literature only

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