ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.1814C>T (p.Thr605Ile)

gnomAD frequency: 0.00103  dbSNP: rs112388307
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426949 SCV000518725 likely benign not specified 2015-09-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000874720 SCV001016938 likely benign LAMA2-related muscular dystrophy 2024-01-24 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001288666 SCV001475944 uncertain significance not provided 2019-11-06 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001288666 SCV003816312 likely benign not provided 2023-07-20 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004532988 SCV004740250 likely benign LAMA2-related disorder 2023-01-13 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001288666 SCV001550932 uncertain significance not provided no assertion criteria provided clinical testing The LAMA2 p.Thr605Ile variant was not identified in the literature nor was it identified in GeneInsight-COGR, Cosmic, and LOVD 3.0. The variant was identified in dbSNP (ID: rs112388307) and ClinVar (classified as likely benign by GeneDx). The variant was also identified in control databases in 99 of 282574 chromosomes at a frequency of 0.00035 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 90 of 24970 chromosomes (freq: 0.003604), Latino in 5 of 35432 chromosomes (freq: 0.000141), Other in 1 of 7216 chromosomes (freq: 0.000139), European (Finnish) in 1 of 25030 chromosomes (freq: 0.00004), European (non-Finnish) in 2 of 129026 chromosomes (freq: 0.000016), while the variant was not observed in the Ashkenazi Jewish, East Asian, and South Asian populations. The p.Thr605 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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