ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.955G>A (p.Val319Ile)

dbSNP: rs1393510784
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366506 SCV001562808 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 319 of the MKS1 protein (p.Val319Ile). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1057511). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MKS1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
New York Genome Center RCV002468239 SCV002764402 uncertain significance Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28 2021-10-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV004036974 SCV004974956 uncertain significance Inborn genetic diseases 2022-10-06 criteria provided, single submitter clinical testing The c.955G>A (p.V319I) alteration is located in exon 10 (coding exon 10) of the MKS1 gene. This alteration results from a G to A substitution at nucleotide position 955, causing the valine (V) at amino acid position 319 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001831269 SCV002087638 uncertain significance Meckel syndrome, type 1 2020-08-31 no assertion criteria provided clinical testing

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